Insulin-Induced Gene 1‑Enhance Secretion of BMSC Exosome Enriched in miR-132–3p Promoting Wound Healing in Diabetic Mice

• Published in: Molecular pharmaceutics 2024-09, Vol.21 (9), p.4372-4385
• Main Authors: Zheng, Liming, Song, Honghong, Li, Yang, Li, Hengfei, Lin, Guanlin, Cai, Zhenyu
• Format: Article
• Language: English
• Subjects: Animals; Cell Movement; Cell Proliferation; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - therapy; Exosomes - metabolism; Fibroblasts - metabolism; Male; Mesenchymal Stem Cells - metabolism; Mice; Mice, Inbred C57BL; MicroRNAs - genetics; MicroRNAs - metabolism; Wound Healing
• ISSN: 1543-8384; 1543-8392; 1543-8392
• DOI: 10.1021/acs.molpharmaceut.4c00322

Chronic diabetic wounds represent a significant clinical challenge because of impaired healing processes, which require innovative therapeutic strategies. This study explores the therapeutic efficacy of insulin-induced gene 1-induced bone marrow mesenchymal stem cell exosomes (Insig1-exos) in promoting wound healing in diabetic mice. We demonstrated that Insig1 enhanced the secretion of bone marrow mesenchymal stem cell-derived exosomes, which are enriched with miR-132–3p. Through a series of in vitro and in vivo experiments, these exosomes significantly promoted the proliferation, migration, and angiogenesis of dermal fibroblasts under high-glucose conditions. They also regulated key wound-healing factors, including matrix metalloproteinase-9, platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor-β1, and platelet endothelial cell adhesion molecule-1, thereby accelerating wound closure in diabetic mice. Histological analysis showed that Insig1-exos were more effective in promoting epithelialization, enhancing collagen deposition, and reducing inflammation. Additionally, inhibition of miR-132–3p notably diminished these therapeutic effects, underscoring its pivotal role in the wound-healing mechanism facilitated by Insig1-exos. This study elucidates the molecular mechanisms through which Insig1-exos promotes diabetic wound healing, highlighting miR-132–3p as a key mediator. These findings provide new strategies and theoretical foundations for treating diabetes-related skin injuries.